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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 2 - Biochemistry (E. Izaurralde)     Display Documents



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ID: 695238.0, MPI für Entwicklungsbiologie / Abteilung 2 - Biochemistry (E. Izaurralde)
Structure of the PAN3 pseudokinase reveals the basis for interactions with the PAN2 deadenylase and the GW182 proteins
Authors:Christie, M.; Boland, A.; Huntzinger, E.; Weichenrieder, O.; Izaurralde, E.
Date of Publication (YYYY-MM-DD):2013-08-08
Title of Journal:Molecular Cell
Journal Abbrev.:Mol Cell
Volume:51
Issue / Number:3
Start Page:360
End Page:373
Sequence Number of Article:23932717
Review Status:Internal review
Audience:Experts Only
Abstract / Description:The PAN2-PAN3 deadenylase complex functions in general and miRNA-mediated mRNA degradation and is specifically recruited to miRNA targets by GW182/TNRC6 proteins. We describe the PAN3 adaptor protein crystal structure that, unexpectedly, forms intertwined and asymmetric homodimers. Dimerization is mediated by a coiled coil that links an N-terminal pseudokinase to a C-terminal knob domain. The PAN3 pseudokinase binds ATP, and this function is required for mRNA degradation in vivo. We further identified conserved surfaces required for mRNA degradation, including the binding surface for the PAN2 deadenylase on the knob domain. The most remarkable structural feature is the presence of a tryptophan-binding pocket at the dimer interface, which mediates binding to TNRC6C in human cells. Together, our data reveal the structural basis for the interaction of PAN3 with PAN2 and the recruitment of the PAN2-PAN3 complex to miRNA targets by TNRC6 proteins.
Free Keywords:Adenosine Triphosphate/metabolism; Amino Acid Sequence; Animals; Autoantigens/chemistry/*metabolism; Binding Sites; Carrier Proteins/*chemistry/*metabolism; Crystallography, X-Ray; Exoribonucleases/*metabolism; Humans; MicroRNAs/genetics; Molecular Sequence Data; Protein Multimerization; Protein Structure, Tertiary; RNA/metabolism; RNA Stability; RNA-Binding Proteins/chemistry/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:root
Affiliations:MPI für Entwicklungsbiologie/Abteilung 2 - Biochemie (Elisa Izaurralde)
Identifiers:ISSN:1097-4164 (Electronic) 1097-2765 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/23932717 [ID No:2]
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